TY - JOUR T1 - Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation JF - Thorax JO - Thorax SP - 770 LP - 777 DO - 10.1136/thx.2008.104133 VL - 64 IS - 9 AU - L A Borthwick AU - S M Parker AU - K A Brougham AU - G E Johnson AU - M R Gorowiec AU - C Ward AU - J L Lordan AU - P A Corris AU - J A Kirby AU - A J Fisher Y1 - 2009/09/01 UR - http://thorax.bmj.com/content/64/9/770.abstract N2 - Background: Aberrant epithelial repair is a key event in the airway remodelling which characterises obliterative bronchiolitis (OB) in the transplanted lung. The potential for airway epithelium from lung transplant recipients to undergo epithelial to mesenchymal cell transition (EMT) was assessed in culture and in vivo in lung allograft tissue.Methods: Change in epithelial and mesenchymal marker expression was assessed after stimulation with transforming growth factor β1 (TGF-β1) alone or in combination with tumour necrosis factor α (TNFα) and compared with untreated controls. The ability of cells to deposit extracellular matrix, secrete matrix metalloproteinases (MMPs) and invade collagen was investigated. Immunolocalisation of epithelial and mesenchymal markers was compared in airway tissue from stable recipients and those with OB.Results: Untreated cells maintained epithelial morphology and phenotype. TGF-β1 reduced expression of epithelial markers, increased expression of vimentin and fibronectin, promoted collagen I and fibronectin deposition and increased MMP-9 production. Co-treatment with TNFα dramatically accentuated phenotypic and some functional features of EMT. Airway epithelial biopsies from recipients with OB demonstrated significantly increased staining for mesenchymal markers and significantly reduced E-cadherin staining compared with stable recipients.Conclusions: These observations demonstrate the ability of human airway epithelium to undergo EMT and suggest this phenomenon may be a potential link between inflammatory injury and TGF-β1-driven airway remodelling in the development of OB. ER -